A series of quantitative microscopic studies which have been completed in this laboratory has demonstrated that in schizophrenic brain there is no evidence for a process of neuronal degeneration in the prefrontal, anterior cingulate or primary motor cortex. The evidence does suggest, however, that novel cytoarchitectural variations, particularly in anterior cingulate cortex, may occur in relation to this disorder. In the region of layer II of the cingulate cortex, there may be a unique structural variation in which there are smaller domains or aggregates of neurons with a diameter of approximately 300 microm, as well as greater numbers of long, vertical axons which may be associative in nature. This proposal describes a series of quantitative morphometric and immunocytochemical studies of the cerebral cortex which aim to replicate and extend these earlier studies in a new cohort of schizophrenics to test the reliability of these findings. In addition, patients with psychosis in the setting of primary effective disorder will also be studied, so that the effects of long-term psychosis and/or neuroleptic exposure can be evaluated. The studies to be done include: a) determinations of cell counts and neuronal cell size; b) computer-assisted analyses of the spatial arrangement of neurons along distances ranging up to 400 microm; c) three-dimensional reconstructions of tracings of neurons, and possibly axons, in order to determine whether macrocolumnar differences in anterior cingulate cortex may occur; d) quantitation of immunocytochemical reaction product for markers of axons, dendrites and functional synapses by either microdensitometry or manual counting.